CS243456B2 - Male anthers' sterilization agent and method of its efficient substance's production - Google Patents

Abstract

A method of sterilising the male anthers of a plant, which comprises applying to the plant an azetidine derivative which is an acid of the general formula I or a salt and/or an ester, amide, alkylamide, hydrazide or alkylhydrazide thereof: in which:

• X represents one of the groups CH₂, CHR or CR₂;
• Y represents one of the groups CHR, CR₂ or CH·CO₂H;
• Z represents one of the groups CH₂, CHR, CR₂ or CH·CO₂H;

the or each R independently represents an alkyl, alkenyl or cycloalkyl group or an aryl or aralkyl group optionally substituted on the aryl nucleus by one or more of the same or different substituents selected from halogen atoms, alkyl groups and alkoxy groups; and one but only one of Y and Z must represent a CH·CO₂H group.

Description

The present invention relates to a composition for sterilizing male anthers and to a process for the manufacture of an active ingredient thereof. The composition according to the invention is primarily intended for obtaining F 1 hybrid seeds. In order to obtain F, hybrid seeds, which have numerous advantages over non-hybrid seeds, seed growers carefully cross-pollinate selected parent plants. In plants that have hexraafrooite blooms and normally self-autoclave, as in the case of small grain cereals, this is accomplished by manually removing the male anthers from each flower. It is an operaai that is extremely demanding on Sas and requires highly skilled workmen. Bjflo has therefore devoted considerable research efforts to the treatment of chemicals that can be dooditi. - the same result.

SUMMARY OF THE INVENTION The present invention provides a composition for sterilizing male anthers of plants. This composition together with the carrier comprises the active ingredient an azetidine derivative of the formula I

(I>

where

X is CHg,

X represents a group of the formula CHR, CHCOOH, CHCOOH3 or CHCO3HR3,

OF . represents a group of the formula CHg or CHCOOH, with the proviso that only one of the symbols. Y and Z may be CHCOOH in which

R is C 1 -C 4 alkyl,

R 1 represents a C 1 -C 4 alkyl group, a benzyl group or an alkali metal atom, and znamená 2 represents a cyclohexyl group, or an N-hydrohalide salt thereof.

Substituent R represents an alkyl group having 1 to 4 carbon atoms. R is methyl or ethyl.

Preferably X is CH 8, Y is CHR or CHCOOH and Z is CH 2 or CHCOOH, wherein either Y or Z is CHCOOH

The azetidine derivative forming the active ingredient of the composition of the invention may be either a free acid of the formula I or a hydrohalide salt thereof. For the purposes of the present invention, the azetidine derivative both in the free acid form and in the hydrohalogenic form is preferably dtf.

A particularly preferred azetidine derivative is 3-aryridine and 2-carbine (oцfyЗччmУУlavt)

The azetidine derivative may be in the form of isomers depending on the meaning of the groups X, Y-Z Z. For example, 2-carboxy-3-reyeylaeeeidine exists in the form of geomeric isomers depending on the relative position of the carbonyl β methyl group β in addition of these geomeric isomers there is an optical isomer. It is evident in processes involving biological systems that some isomers may be more active than other isomers, and so is the method of the invention.

Using the composition of the present invention, plants in which tulle is formed by male sterility, without substantial effect, are not female sterility. The composition is preferably used in cereals such as maize and millet, especially small grain cereals such as peas and barley, preferably when the plant is in a growth stage between late offshooting and cob planting. The active ingredient is effectively applied at a rate of from 0.05 to kg / ha, preferably from 0.25 to 1 kg / ha.

Using the composition of the present invention, production of F, a hybrid seed that includes cross-pollination of the tulle treated plant with the composition of the present invention, with a second plant of a different strain can be achieved.

The azetidine derivative is preferably formulated as an ophthalmic agent (sometimes also referred to as a preparation). As already mentioned, such a pollination suppressant composition comprises a compound of formula (I) and / or an N-hydrohalide salt thereof together with a suitable carrier.

Most azetidine derivatives are new. Accordingly, the present invention relates to a novel azetidine derivative which is an acid of formula (I) above, or a hydrohalide thereof, except that when Y represents a group of formula CHCl 3 or CHCOOH, then X has the group CH ₂ .

A preferred novel azetidine derivative is 3-yeyl-2-Oarioisyl.

The present invention further provides a process for the preparation of an azetidir derivative as an active ingredient of a composition comprising the step of hydrolyzing or alcoholizing a deprotecting cyano group wherein the nitrogen atom at the 1-position is protected with a benzyl or benzyl group. to form an azetidine derivative in which Z represents a group of formula^CHg and^potom se benzylov^and or^be] ^ 2 ^ Jj^j^ (^ x^r^: Hunting^and the group removed from azetidiriv by hydrogenation with hydrogen in the catalyst.

The process may be carried out pooUití kteréhokooi known process for converting the amino ^ ^ ^ upi ^y at the carboxy group. tydrolýzu may be done on a case ^{p b} uso tions in ^Copper acid or alkali to kianosloučeninu, suitably under mild conditions by formation of a derivative of an azetidine in free acid form or its sooi. Alcoholysis can be carried out by boiling tyanoolouč ^e N in Z ^ ^yp sLex reflux in an alcohol under mnoo ^ i ^ ^ i ^ c orovcd dry ^^ ^No IMZ arises in derirát azttiiinu ^f Orme ester or tydrochloridu.

If the presence of the protector is a slkipina ,. it is possible to tuto ^^^ εοΙ! in an appropriate way. A particularly suitable protecting group is a benzyl group which can be detached from the azetidine ring from mild conditions by reaction with hydrogen gas in the presence of a catalyst, for example palladium or palladium hydroxide to carbon.

The cyano compound can be prepared, for example, by reacting the corresponding hydroxy compound and the sulfide chloride to give the 3-ethylsulfonyl azididine analog and reacting it with an alkali metal cyanide, preferably sodium cyanide. The 1-hydroxy compound may be prepared by reaction of a lalogylethyloxy with a primary amine.

and

The carrier in the composition according to the invention is any one of the compounds where the active ingredient is combined to effect application to the plant to be treated, or for storage, transport or maladaptation. Carriers It may be a solid or a liquid, including a material which is usually gaseous, but which is compressed to form a liquid, and any of the carriers used in the formulation of the low-viscosity preparations. ,

Aqueous solid carriers include natural and synthetic clays and silicates, for example, natural silicates, such as gelatin clays, magnesium silicates, for example talc, silicone silicates, for example attapulgites and verniktiulty, aluminum silicates, e.g. calcium carbonate, calcium sulphate, synthetic hydrated oxides and synthetic systems, for example, cumronic resins, polyvinyl chloride and styrene polymers, copolymers, solid polyphenols, resins, waxes, for example beeswax, paraffin wax and chlorinated mineral waxes. , and solid fertilizers such as superphosphates.

Suitable liquid carriers include water, alcohols, for example, itopiopropyl alcohol and glycols, ketones, for example, acetone, methyl, methyl, meryl isobutyl ketone and cyclohexanone, ethers, aromatic or trivalent hydrocarbons, for example benzene, toluene and xylene, petroleum fractions, for example kerosene and light mineral oils, chlorinated hydrocarbons, such as УрУrechLo-methane, perchlorethylene and trichlorate. Mixtures of different fluids are often suitable.

The lime products are often mixed and transported in a concentrated form, which is then diluted by the user before use. The darkness of my minions. The surfactant is facilitated by this process. Thus, preferably at least one of the carriers of the composition of the invention is a surfactant. For example, the composition may contain at least two carriers, at least one of which is a surfactant.

The surfactant may also be of a non-ionic or ionic nature. Examples of suitable powder active agents include sodium or calcium salts of polyacrylic acids and lignin sulphonic acids, condensation products of matic acids or aliphatic amines or amines containing at least 12 carbon atoms in the molar oil, and ethylene oxide and / or propylene oxide, fatty acid esters. glycell, sorbitol, sucrose or pentaethythrite, their condensates with ethylene oxide and / or propylene oxide, condensation products of a fatty alcohol or altylphenols, for example p-octylphenol or p-octylcresol, β ethylene oxide and / or propylene oxide, sulphates or sulphonates of these condensation prodrugs metal or alkaline earth metal, preferably sodium salt, sulfuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium, secondary sodium sulphate, sodium salt of sulphated castor oil and sodium, for example sodium iodinebenzinobutyric acid And polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide. >

The formulations of the invention may be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, cans, suspension concentrates and aerosols. the powders usually comprise 25, 50 and 75% by weight of the active ingredient and usually contain, in addition to 3 to 10% by weight of a dispersion and, if necessary, up to 10% by weight of a stabilizer or stabilizers and / or other additives, for example penetration agents or adhesives. The powders are generally formulated as a dust concentrate of similar composition to that of a lethal powder, but without a dispersant, and are diluted into a longer solid carrier to form a mixture containing usually 0.5 to 10% (mono-percent) of the active ingredient. The granules are usually prepared between 1.676 and 0.152 mm in size and can be prepared by aolotteration or ХтргедагёпС technique. Grunules typically contain 0.5 to 25% himt. active ingredients and 0 to 10% by weight of additives such as stabilizers, slow release moodficitors and surfactants;

AND

The emulsifiable concentrates usually additionally contain a solvent and, if necessary, an even longer solvent, 10 to 15% w / v active ingredient, 2 to 20% w / v other additives such as stabilizers, penetration agents and corrosion inhibitors. Suspension concentrates are generally formulated to provide a solid, non-sedimenting liquid product, and typically contain from about 10% to about 75% active ingredient, from about 0.5% to about 15% dispersant, from about 0.1% to about 10%, with successful agents such as protective colloids and thixotropic agents, 0 to 10% by weight of other additives, for example antifoams, corrosion inhibitors, stabilizers, penetrating agents and binders, and water or an organic liquid in which the active ingredient is substantially insoluble, some organic solids or inorganic salts may be dissolved in to prevent sedimentation or as freezing agents ·

Aqueous dispersions and emulsions, for example formulations obtained by diluting a wettable powder or concentrate according to the invention with water, are within the scope of the invention. Said emulsions may be of the water-in-oil or oil-in-water type and may be of dense mayonnaise consistency.

The compositions of the invention may also contain other ingredients, for example other substances, with injecticidal, herbicidal and fungicidal properties.

The following examples illustrate the invention.

He did

Preparation of 3-ethyl-2-carboxyasetidine (a) 6.5 g (0.065 mol) of 4-methyltetrphydrofuran-2-one and 0.4 g of red phosphorus were mixed together and heated to a temperature between 100 and 115 ° C. Sasha was reacted with 30 g (0.18 mol) of bromine until a hydrogen bromide evolved. The reaction mixture was then cooled to 0 ° C to 5 ° C, 36 g (0.3 mol) of benzyl alcohol was added, and the mixture was saturated with anhydrous hydrogen chloride. The resulting mixture was weaned for 24 hours. 100 ml diethyl ether was added and the mixture was poured into a 3% aqueous solution of sodium bicarbonate containing ice. The slurry was extracted several times with diethyl ether. The ether extracts were dried over anhydrous magnesium sulfate and evaporated. The residual yellow oil was subjected to vacuum distillation: all liquids boiling at a temperature of up to 122 ° C at 80 Pa were removed. 15 g of the residue was subjected to NMR spectroscopy. That it is a benzyl ester of the acid

1,3-di-bron-2-methyl butane, obtained in 66% yield.

Analysis for ₂ calculated: C 41.1 H 4.0 Br 45.7 found: C 44.1 H 4.5 Br 44.6 (b) A mixture of 15.0 g (0.043 mol) of the dibromester obtained according to (a) 27.8 g (0.13 mol) of ol-phenylbenzylamine and 250 ml of acetonitrile were heated to reflux for 24 hours. The resulting mixture was filtered, evaporated to dryness, triturated with ether (200 mL) and filtered again. The aged solution was then charged with dry hydrogen chloride for 5 minutes. The colorless tulle obtained is isolated, suspended in 300 ml of chloroform and reacted with a small excess, i.e. 20 ml of triethylamine. The resulting clear solution was evaporated to dryness and extracted with diethyl ether. The ethereal solution obtained was evaporated to give 10 g of an oil which was chromatographed on a silica gel column using a 1.5: 8.5 mixture of ethyl acetate and petroleum ether (b.p. 60-80 ° C). Evaporation of the first fractions yielded an oil which solidified on standing. It was recrystallized from ethanol to give 2.2 g of 1-diphenylmethyl-2-carboxy-3-methyl-azetidine benzyl ester, m.p. 101-110 ° C.

'1

Analysis calculated for C25 H25 N2 O: C: 80.8 H: 6.8%: 3.8%. Found: C: 80.2%: 6.8%: 3.6%.

(c) 2.0 g (0.0054 mol) of the cyclic ester of (b) was suspended in 500 ml of ethanol and 20 ml of methanol, 0.5 g of 5% palladium on carbon catalyst was added, and the mixture was hydrogenated in a Perr apparatus at a hydrogen pressure of between 300 to 400 kPa for 15 hours. The mixture was filtered and evaporated. Diethyl ether was added and the aqueous phase was extracted several times and then evaporated to dryness to give 0.5 g of a colorless solid which was recrystallized from ethanol to give 2-carboxy-3-aetylezetidine, m.p. 200-101 ° C. decomposition, in 03% yield.

Analysis for C ^ H ^ MO ₂ Calculated C: 52.17 H: 7.8 N: 12.17% Found C: 51.2 H: 8.2 ji: 11.9%.

The HMR-spectrum showed that the substance was a 9: 1 mixture of geometric isomers ·

Example 2

Preparation of 3-carboxyazetidine (a) 15 g (0.06 nol) of 1-diphenylmethyl-3-cyanoazidine were mixed with 150 ml of 2-methoxyethanol and added to a solution of 13 g (0.2 nol) of sodium hydroxide in 10 The resulting mixture was heated to reflux for 15 minutes, during which time it produced ammonia, and was then poured into 1500 ml of water and ice. The mixture was then acidified with dilute hydrochloric acid to pH 1.5 and then extracted with dichloromethane. The pH of the aqueous solution was adjusted to 5 by adding solid sodium bicarbonate to the stirred solution.

After about 0.5 hours, 1-diphenylmethyl-3-carboxyazetidine precipitated out of solution as a fine colorless substance. The solid was collected, washed with water and air dried. 13 g was obtained, corresponding to a yield of 81. The melting point was 190-191 ° C with decomposition.

Analysis: Calculated: C: 76.4 H: 6.4 N: 5.2 *, found: C: 75.4 H: 6.4 X: 5.1% · (b) 10 g (0.037 mol) M -eubatitated acid according to (a) was suspended in 300 ml of methanol and 6 g of catalyst and palladium hydroxide on carbon prepared by the method described in Tetrahedron Lettera, 1967, p. 1663 were added. The mixture was hydrogenated in a Parr hydrogenator under hydrogen pressure and 360 kPa for 3 hours · Hydrogen uptake stopped suddenly after 1 hour · The solution was filtered and evaporated to near dryness under reduced pressure · The aqueous residue was extracted several times with dichloromethane and then evaporated to dryness · The colorless residue was recrystallized from ethanol to give 2.6 g of glossy hydrated 3-carboxyasetidine plates with a melting point of 169-170 ° C and decomposition.

Analysis calculated for C: ^H ^OOO.: C: 40.3H: 7.5X: 11.7 M, found: C: 40.3H: 6.7X: 11.6

Evaporation of the tarretalizing agent provided additional crystalline material in an amount of 1.2 g, m.p. 235 DEG-270 DEG C. with decomposition. These crystals consisted of anhydrous 3-carboxyazatidine and had identical NMR spectrum with hydrated cresine. Total yield of step (b) tulle 95%

Example 3.

Preparation of 3-ethyl-22-carboxyazetidine (a) 21 g (0.132 aol) broccyl was added to stirred gangrene 15 g (0.132 aol) 4-ο1 $ 1 · -

butyrolactone and 0.3 g of Red Phosphorus were maintained at 120 ° C. Bro * tyl přL-.

given just below the reaction surface. laneea and during the final stage of broauyl addition, the development of hydrogen bromide was observed. The reaction mixture was cooled, 40 [mu] l of bainzanol was added, and the softened tulle solution was saturated with anhydrous hydrogen chloride gas at room temperature. The soaked tulle was allowed to stand for 24 hours. Saesa tulle potoa divided between ether and ros, flow sodium sodium bicarbonate with the ether layer of tulle separated and dried over magnesium sulphate. The dried solution was washed with 2-taroa-3-bromoalpentanoic acid cesine ester (boiling point 149 DEG C./93 Pa) in 43% yield.

t.

Analysis for ^C 13 ^H * 1 ° 2 ° 2 Calculated: C 42.9 H 4.4 Br 44.0% Found: C 43.5 H 4.5 Br 43.3%.

(b) 19.5 g (0.054 aol) of the dibro-α-atex obtained in accordance with (a) and 29 g (0.16 aol) of irим ^ ПгУ · anirn in acetonitrile were stirred and heated to boiling for a period of time 48 hours. The resultant dream was cooled, freed from the insoluble salt by filtration, and the filtrate evaporated to dryness. The residue, which represented a complex saesse of products, was partially loaded on a column with ailikagoLaa in anthylacatate / patrolatar as a eluent. The first fractions of the tulle were evaporated, evaporated to dryness, whereby the tulle was obtained with 1-diphenyl-ethyl-2- (methyl) -benzyl-2-methylbenzamide as a constituent (65% yield by Peace) and 8 g of the remaining crude gangrene. ' (c) 8 g of the crude ester obtained according to (b), 100 Λ 1 of ethanol and 10 g of a 5% palladium catalyst, not hydrogen, were tydrogenated at temperature and carried under hydrogen pressure.

300 to 400 kPa for 10 hours in Parrov behind the pan. The resulting salt was evaporated to dryness and partitioned between methylene chloride and water. The aqueous phase of the tulle was separated, concentrated by evaporation, and loaded onto a Dowex 8-50x (H) column. . Isolation iaiaotyaeliay Tyl performed by eluting the column with 2M roztokea Baobab By steaming protah ^ SITUATIONS extracts poatytlo colorless solid * substance which, upon přelomytalování from ethanol ^p ředstavove! And iso * n] m ^d sněa L ^Ia: 3 ^Q 3-ethyl-2-karboэχr1azaidiau.

Analysis for C: CH ^NOg requires C: 55.8 H: 8.5 N: 10.85%, found: C: 55.8 H: 8.8 N: 10.7%.

Additional 3-atyl-2-trans-azazidine was added to evaporate the lye liquors after tamalization.

of different composition of the isoaer gangrene {2 <xx3eJ. [

I Analysis.?

Found: C, 55.8; H ^, 8.9; N ^, 10.7%.

and

J

Demonstration of pollination suppression efficiency

Spring wheat, a variety of Sicco, was sown in a greenhouse in 13 cn pots to compost the ground. A high-pressure mercury vapor lamp was added to provide a cointant daytime of 16 hours. The temperature was maintained at approximately 20 ° C.

Example 4

The substance was in the form of an aqueous solution containing 0.1% nonldet P 40 (trade mark) as a wetting agent and 1% acetone to facilitate dissolution. This tulle is diluted with water to the end of xtracX 1000 ppm and sprayed onto the plants · Botlin tulle treated at the growth stage when the tulle is detectable just the second node of the plant.

On the emergence of the ears just before anesthesia, 5 peaks from each treated pot were placed in cellophane bags to avoid cross-pollination. When the ear tulle was matured in the bags, the harvested tulle seeds were evaluated and compared with untreated controls.

The results are shown in the table below.

Table

Example compound Xnhbice Grain Handles (% Control) 1 69 2 87 2 [2α: 3β] 68

It can be seen that the test compounds showed a significant reduction in seed batch compared to the untreated control, which clearly illustrates the ability of the compounds to sterilize male anthers.

Claims (3)

Composition for the sterilization of male anthers in plants, characterized in that they contain, together with a noaic agent, an azatidine derivative of the general formula (X): X is CH »» X is CHa, CHCOXH, CHCOOB4 or CHCO1QQB, Z is CH 3 or CHCOOH, with the proviso that only one of X and Z can represent CHCO 3 H in which: R represents an alkyl group having 1 to 4 carbon atoms, R @ 1 represents a C1 -C4 alkyl group, a benzyl group or an alkali metal atom and R 8 represents a cyclohexyl group, or an N-hydrothelide salt thereof. 2. A composition according to claim 1, wherein the active ingredient comprises a compound of formula I in the free keel form, wherein X is CHCOOH and X and Z each denote a group CH3; 3. A process for the preparation of an azetidine derivative as active ingredient of the composition of claim 1, which comprises reacting a corresponding cyanoalucine whose nitrogen atom in position 1 is protected with a benzyl or benztydyl group, hydrolyzing or alcoholizing to form an ezetidine derivative in which Z represents and then the benzyl- or benzhydryl group is removed from the ezetidine ring by hydrogenation with hydrogen gas in the presence of a catalyst.